Nielsen PB, Larsen TB, Skjoth F, et al. Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation. JAMA Intern Med. 2017 Feb 20. doi: 10.1001/jamainternmed.2016.9369.
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Importance: The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists.

Objective: To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH).

Design, Setting, and Participants: This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge.

Exposures: No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure.

Main Outcomes and Measures: One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use.

Results: A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke or SE (AHR, 0.40; 95% CI, 0.15-1.11); however, in contrast to patients with hemorrhagic stroke, therapy resumption was associated with a significantly lower rate of recurrent ICH (AHR, 0.45; 95% CI, 0.26-0.76). A reduction in mortality was associated with resuming warfarin therapy among patients with hemorrhagic stroke (AHR, 0.51; 95% CI, 0.37-0.71) and those with traumatic ICH (AHR, 0.35; 95% CI, 0.23-0.52).

Conclusions and Relevance: Resumption of warfarin therapy after spontaneous hemorrhagic stroke in patients with AF was associated with a lower rate of ischemic events and a higher rate of recurrent ICH. Among patients with a traumatic ICH, a similar lower rate of ischemic events was found; however, a lower relative risk for recurrent ICH despite resuming warfarin treatment was also revealed.

Comments from MORE raters

Physician rater

Although the authors attempted to control for major factors including comorbidities and severity of illness, there are likely confounding variables present that limit the ability to draw conclusions. Mainly, it seems just as likely that being able to restart warfarin is a marker for better health status as it is that restarting warfarin reduces mortality.
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